KR20140070946A - fermentation extracts of the oriental herbal mixtur - Google Patents

Abstract

The present invention relates to a pharmaceutical composition comprising a Kochiae fructus, Psidium guajava, and hollyhock mixture extract, extracted with water, alcohol, or aqueous alcohol solution, as an active ingredient for alleviating or treating acne dermatitis. The pharmaceutical composition of the present invention can be valuably used for alleviating and treating the acne dermatitis since the composition can effectively alleviate or treat acne symptoms by having effects of alleviation of acne, alleviation of erythema, skin regeneration, antibacterial, and skin soothing by controlling immune inhibitory ability and secretion of cytokine.

Description

[0001] The present invention relates to a herbal mixed fermentation extract and a pharmaceutical composition containing the extract as an active ingredient.

The present invention relates to a pharmaceutical composition for improving or treating acne dermatitis containing mixed fermentation extract and an effective ingredient thereof. More specifically, it relates to a pharmaceutical composition for improving or treating acne dermatitis, which comprises fermented and extracted fermented water, ethanol, or methanol, The present invention relates to a pharmaceutical composition for improving or treating acne dermatitis containing an effective ingredient of a fermented extract of the present invention.

The present invention relates to a pharmaceutical composition for improving or treating acne dermatitis, which comprises as an active ingredient, a golden mixed fermented extract of golden pomace, soybean paste, cinnamon, yuukee, sycamore, pestilent, , And more specifically, a mixed fermented extract and an active ingredient thereof, which are extracted from water, ethanol or methanol as an extraction solvent, and include goldfish, soybean paste, cinnamon, yuukee, sorghum, To a pharmaceutical composition for improving or treating atopic dermatitis. The inventor of the present invention refers to a natural fermentation extract as a natural arc complex, which includes golden pomace, soybean paste, cinnamon, yuukee, sycamore, pest control, Acne (acne vulgaris, acne) refers to the sebaceous glands and inflammatory diseases of the skin. It usually appears red on the skin, but there are about 50 types. Humans come to puberty a lot. Incorrect makeup, stress, sex hormones, Demodex fungus are the factors of acne. Acne is prone to sebaceous secretions. Acne begins with pimples that secrete sebum. It is called black acne (the state where the pore is opened and the content is visible) or the white acne (the pore is closed state) where sebum and keratin gather in the pore. It is the skin-resident bacterium P. acnes that turns black or white acne into red acne. Because it likes sebum, it stimulates proteins that proliferate in the pores and cause inflammation in the skin. Therefore, inflammation occurs, reddening or pus is piled up with yellow parts. More progress can be made here, and secretions from the pores can spread and the inflammation spread. At this time, the deep part of the skin will be damaged, so that even if the inflammation improves, the traces may remain. In addition, the structure of acne is not completely explained. Because of confectionery products like chocolate or sexual activity

There is rumor that it will happen, but it has not been scientifically proven. What happens during puberty is usually due to the increased secretion of testosterone.

For most people, the response is diminished over time. Acne is a skin disease that has been used since 1925 when Coca has been known to have a tendency to develop dermatitis, asthma and fever fever as a result of an allergic reaction to hormones, foods and inhalants, In addition to dermatitis, asthma, allergic rhinitis, allergic conjunctivitis and the like. Atopy is accompanied by an allergic reaction, among which acne dermatitis is a chronic or recurrent dermatitis, characterized by the characteristic shape and distribution of skin lesions and the birth of an individual or family with an acne history, ie acne constitution (genetic predisposition) Is a very common skin disorder. Acne dermatitis usually begins in infancy and early childhood, especially about two months after birth, with about 50% occurring before 2 years of age and symptoms occurring almost 5 years of age, but rarely in adults. Most of the symptoms, along with growth, are alleviated or disappear, and more than half of the infantile patients develop before 2 years of age. Acne dermatitis accompanies severe itching

It begins with an erythematous papulopenia and epiglottis and progresses to acute symptom with blistering and serous effusion and sloughing when it gets worse. The most characteristic symptom, pruritus, is so severe that it scatters to the point of bleeding, and continues to worsen with a vicious cycle of itching - scratching - itching, and the longer the skin thickens and wrinkles become apparent. Most clinical manifestations are caused by scratching or rubbing, and at night, pruritus becomes more severe and causes sleep disturbances. Recently, the incidence of acne dermatitis has been increasing worldwide, which is attributed to air pollution, increased exposure to antigens due to changes in the residential environment, decreased breastfeeding, and decreased pediatric infectious diseases . According to a national epidemiological survey conducted by the Korean Academy of Pediatrics Allergy and Respiratory Society in 1995, 12 ~ 24% of elementary school children and 6 ~ 8% of middle school students were diagnosed with acne dermatitis. In 2000, 24.9% of elementary school students, 12.8% were diagnosed with acne dermatitis, and the incidence of adult acne dermatitis was also increasing in Korea

have. Although the exact pathophysiology of acne skin disease has not yet been fully understood, it is thought that immunological and non-epidemiological mechanisms are involved with genetic predisposition. There are many reports that extrinsic acne dermatitis, which accounts for the majority of acne dermatitis, is caused by immune mechanism associated with immunoglobulin E (IgE), and primary immune response due to T-cell abnormality is involved rather than secondary immunity to specific allergens. In the case of acne dermatitis, cell-mediated immune dysfunction is associated with an increase in immunoglobulin E, and there are reports that primary immune response is involved in the pathogenesis of acne dermatitis in addition to secondary immunity (Lee, Ki Young, , Korean Medical History, Seoul, 2001, pp23 ~ 52). In acne dermatitis patients, cell-mediated immunity disorder is known to occur up to 80%, and susceptibility to skin infections due to viruses and dermatophytes is increased and susceptibility to contact allergens tends to disappear. In the past, T-cell maturation deficit, CD8 + suppressed T-cell

But the role of CD4 + T-cells has recently become more important. That is, T-cells that secrete interleukins 4 and 5, which induce or promote the production of immunoglobulin E from B cells, and interleukin 6, which amplifies, are Th2 cells in CD4 + T-cells, And Th2 cells were found to be highly present. These cytokines stimulate immune cells such as mast cells, macrophages and basophils to promote secretion of histamine, leukotrien, prostaglandin, and nitrogen monoxide (NO) These inflammatory mediators are known to promote the inflammatory response of the skin. Another characteristic of acne skin disease is the lack of gamma linolenic acid in the lipids that form the cell membrane of skin cells. gamma

The deficiency of linolenic acid is a phenomenon caused by a defect in synthesis of linoleic acid to gamma linolenic acid due to a deficiency of delta-6-desaturase in the biosynthesis pathway of essential fatty acids. The synthesis can not be regulated and the production of inflammatory mediators becomes higher. In addition, due to deficiency of gamma linolenic acid, abnormality of the structure of the skin lipid membrane causes excessive water leakage, resulting in the breakdown of the skin barrier. Secondary infection such as bacteria occurs at this time. As described above, a therapeutic agent for acne dermatitis has been developed in consideration of the etiology, mechanism, and symptoms of acne dermatitis known so far. As a result, a number of natural or synthetic immunosuppressive agents, antihistamine agents and steroid agents have been developed

. For example, immunosuppressants include Cyclosporin A, FK506 (tacrolimus; Wasik et al., Immunopharmacology 20: 57-61, 1990) and SDZ ASM981 (Pimecrolimus; Grassberger et al., Br. Dermatology 141: 264-273, 1999). On the other hand, steroids and antihistamines used as treatments for acne dermatitis temporarily alleviate the symptoms, but the skin thinning and osteoporosis induction in patients with long-term use of external or oral steroid hormones , And growth inhibition in children, resulting in local and systemic side effects. Therefore, there is no such side effect, and development of a therapeutic agent with excellent efficacy is required. The branch is the name of the seed of Adamsari, and its scientific name is Kochia scoparia. It is distributed in the whole country and its height is 1 ~ 1.5m. It is a herbaceous herb of annuals and it breeds seeds. Leaves are alternate, lanceolate or lanceolate, both ends are narrow and edges are flat. There are 3 Macs. Flowers are yellowish-green or yellowish-green flowers in July-August, and there are no flower peduncle. Bisexuality and female flowers pile together. The fruit runs from September to October with a flat-bottomed follicle (胞 果), which contains one seed. It is used for ornamental, sibiric, edible and medicinal. The young stems and leaves are called geubu seedlings, and they are eaten as herbs or medicinal plants. The seeds are collected around November, dried in water and dried. When you use it as a medicine, you can use it as a hot spring or as a pill or powder. It mainly manages urinary and dermatological diseases. The major component and action was found to be amorphous 1c, which has an affinity action. This is expected to have an excellent effect in the treatment of acne dermatitis because it can suppress allergic reaction as well as suppression of itch. Guava is a sub-tropical plant belonging to the Psidium genus (Myrtaceae) and is widely distributed throughout the world in sub-tropical climate zones. In some tropics, they grow very much in semi-wild conditions. In California and other sub-tropical regions, it is planted as a garden plant due to its commercial importance. Guava is very cold-weathered, shiny green oval-shaped leaves and large shrubs with white flowers. Its fruit is round and its diameter is over 5cm. It contains a lot of hard seeds and the flesh smells like strawberries. Fruits are used for reproduction, juice, jam, etc., and leaves are mainly used as tea. Guava has been used in traditional Chinese folk remedies to treat diarrhea, dysentery, acute gastrointestinal inflammation and contains botanical compounds such as terpenoids, flavonoids and tannic acid. Guava leaves contain a vitamin-like substance called Batamin U, which inhibits gastric acid secretion and promotes the metabolism of the gastric mucosa, thus improving gastric ulcers and the like. Most of all, it has been known empirically that guava leaves have an effect of improving diabetes from a long time ago. As a result of recent researches, it is scientifically proved that guava polyphenol contained in guava leaves inhibits postprandial increase in blood glucose level and prevents diabetes . Guava polyphenols inhibit the action of digestive enzymes that inhibit carbohydrase activity, so some saccharides are not decomposed into glucose and go down to the intestines to be used as intestinal bacteria or excreted outside the body. As a result, the amount of glucose absorbed into the blood in the small intestine is reduced, thereby inhibiting the blood glucose level from rising sharply. In addition, the rapid rise of postprandial blood glucose level is suppressed, so that the blood glucose level does not go down too much, so that the blood glucose level is kept high so that the insulin sensitivity is enhanced. The efficacy component has been found to have the same function as insulin, and the ingredients are found in three components of polyphenol: strictinin, isostrictictinin, and pedunculagin. The main effects were hypoglycemic action, inhibition of αglucosidase enzyme activity in the small intestine, delayed glucose uptake, and blood glucose lowering effects in STZ (streptozotocin) -induced diabetic rats and db / db mice of type 2 diabetic rats The Guava leaf hot water extract was approved by the Korea Food and Drug Administration (KFDA) for functional content at a level that could help control postprandial blood glucose. It is called Althaea rosea Cavanil, and it is called Shingo flower, Deduk flower, Joonghwa flower, Mandy flower, Calligraphy flower. Appearance Height 2.5m. Flowers bloom in June in white, red, pink, black brown, etc., and have fruit like a dish. The medicinal substance is yellow to pale brown, and most of it is broken. The intact petals are 5, the calyx is circular, divided into 5 pieces, each lobe is triangular and covered with statues. The efficacy is called the root of the flower of the safflower, it is the efficacy to lower the fever, clear the blood, have the diuretic effect and remove the inflammation. It treats the blistering of blood, urine, or feces, and treats cystitis, urethritis, skin pruritus, itchy skin and eczema. The flower is called the stamina. It improves the circulation of the blood. It treats the stomach and lower abdomen, treats the urine, and is good for constipation. Stems and leaves are called scales, and Hari, caused by openness, is treated. The inventors of the present invention have observed that natural extracts capable of treating acne dermatitis have been shown to exhibit immunosuppressive ability, suppression of nitric oxide production and cytochalic acid secretion, , It was confirmed that the acne symptom was considerably alleviated as a result of application to actual acne patients. Thus, it was confirmed that a pharmaceutical composition containing an effective ingredient of the present invention of the present invention, guava, and germinated mixed extract can be useful for acne diseases Thus completing the present invention.

It is an object of the present invention to provide a pharmaceutical composition for improving or treating acne dermatitis, which comprises as an active ingredient, a golden mixed fermentation extract of golden pomace, soybean paste, cinnamon, yuukee, sycamore, insect repellent, .

In order to achieve the above object, the present invention provides a fermented extract of gold mixed with a water, an alcohol or an aqueous alcohol solution, soybean curd, cinnamon, yunghi, sycamore, bug kingdom, . In addition, the present invention provides a pharmaceutical composition for improving or treating acne comprising, as an active ingredient, a golden mixed fermentation extract of golden pomace, soybean paste, cinnamon, yuukee, sycamore, insect repellent, . Hereinafter, the present invention will be described in detail. The present invention provides a fermented extract of gold, which is extracted with water, alcohol or an aqueous solution of alcohol, soybean paste, cinnamon, yuukee, sycamore, pest control, When the fermented extract of gold blast, soybean paste, cinnamon, cinnamon, cinnamon, sycamore, bamboo shoots, bamboo shoots, chrysanthemum, desirable. In the case of extracting the golden blended fermentation extract of golden pomace, cinnamon, cinnamon, yuukee, sycamore, pest insecticide, seedling, chrysanthemum, white waxy, yellow, white and golden mixed fermented extract of the present invention with alcohol, the alcohol is methanol, ethanol, isopropyl alcohol , Butanol, and it is more preferable to use methanol or ethanol. In the case of extracting the golden mixed fermented extracts of the present invention with an aqueous alcohol solution, the aqueous alcohol solution contains 50% or more of alcohol . In addition, the present invention provides a pharmaceutical composition for improving or treating acne, which is contained as an active ingredient in a fermented extract of golden blossom, golden pear, cinnamon, yuukee, sycamore, pest control, The pharmaceutical composition can be effectively used for improving or treating acne through immunosuppression, suppression of nitric oxide production, and modulation of cytokine secretion. Experiments were carried out to test the inhibitory effect on immune response, inhibition of nitric oxide production, and inhibition of secretion of cytokines in order to confirm the availability of fermented extracts of golden sprouts, cinnamon, cinnamon, yuguni, spermatozoa, Respectively.

The immune response inhibitory activity of the mixed fermented extracts of Kangwon, soybean, cinnamon, yuukee, ginseng, zygotes, zebu, tea, The mixed fermented extracts showed a 59.8% immunosuppressive activity at the concentration of 5 g / ml, and the immune response was increased with increasing concentration. The inhibitory effect was also gradually increased and showed excellent immunosuppressive effect of 82.4% at the concentration of 100 g / ml.

Based on the results of the above fermented extracts of golden pine, cinnamon, cinnamon, yugaepi, spermatozoa, pest control, pineapple, chinese herbal medicine, The effect was tested. In most of the participants, the symptom was relieved within one week. Major mitigating symptoms were epidermal regeneration effect with alleviation of stratum corneum, reduction of itching and erythema, and reduction of erythema. Therefore, the present invention is also effective in other skin diseases such as acne skin diseases and atopic diseases, such as golden sponges, soybean sprouts, cinnamon, yuukee, sycamore, pest control, Respectively.

Therefore, by reducing the heat of the epidermis by treatment with the gold blast, soybean paste, cinnamon, yuukee, sycamore, pest control, leaflet, chinese herbal medicine, In addition, it was found that the antimicrobial effect showed the immunostimulating effect and the effect of improving the itching and the epidermal regeneration effect of the acne patient. So far, there has been no clear drug development yet, and it is known that there is no toxicity, and it is a medicinal herb that is based on excellent clinical results in chronic immune diseases and acne skin diseases, such as goldfish, soybean, cinnamon, , Chrysanthemum, and golden mixed fermented extract are expected to heal acne dermatitis. The fermented extracts of gold blast, soybean paste, cinnamon, cinnamon, cinnamon, spermatozoa, bamboo shoots, bamboo shoots, And atopic dermatitis. These diseases may include acne dermatitis, allergic dermatitis, eczema, psoriasis, atopy, and the like.

In addition, the composition for treating acne dermatitis, which comprises, as an active ingredient, the golden blossom extract of gold sprouts, soybean sprouts, cinnamon, yuukee, sycamore, pestilent, , A suspending agent, or a stabilizer, and may be used as a raw material for cosmetics, bath products, soaps, pharmaceutical ointments, veterinary medicines or pack products. In addition, the administration method can be generally applied to the affected part, and the preferable administration method can be selected according to the formulation. The daily dose of the composition of the present invention is generally determined depending on the subject to be administered, the method of administration, and symptoms, It is preferable that the fermented extract of golden and golden fermentation is administered in an amount of 1 to 10 mg / kg, more preferably 5 to 10 mg / kg. The number of times of administration is preferably two times a day or more, but the number of times of administration can also be adjusted depending on the symptom level. However, the dosage needs to be varied and can be varied, in particular considering the sperm specificity and weight of the object to be treated, the type and depth of the disease, the nature of the formulation, the nature of the drug administration, and the duration or interval of administration. In order to effectively treat acne, it is important to choose an appropriate external dosage form. Hereinafter, the present invention will be described in detail by way of examples. However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

Example 1 Preparation of Fermented Extract of Golden Rice Mixture, Golden Rice, Cinnamon, Cinnamon, Cinnamon, Cinnamomum cassia, Chrysanthemum, Chrysanthemum, Chrysanthemum, , Cinnamon, cinnamon, cinnamon, cinnamon, bamboo shoots, bamboo shoots, bamboo shoots, waxy wood, white, yellow, and golden mixed fermentation extracts were prepared using the outposts of Chinese cabbage, .

Example 2 Preparation of Fermented Extract of Golden Mixed Rice, Cinnamomum cassia, Cinnamomum cassia L., Rootgrass, Cryptomeria japonica, Quercus mongolica, Chibusata, 100 g of mixed pre-ointment was mixed with 10-fold volume of ethanol, and the mixture was refluxed for 2 hours. The extract was filtered and vacuum dried to obtain 15 g of ethanol extract.

<Experimental Example 1> Measurement of efficacy of fermented extracts of golden pomace, soybean paste, cinnamon, yugunpia, spermatogonium, pest control,

<1-1> Measurement of Immunosuppressive Activity of Bifidobacterium glutamicum, Guava, and Ganoderma sp.

The immune response inhibitory activity was confirmed by a mixed lymphocyte response assay. Briefly, spleen cells were isolated from the spleen of BALB / c mice and C57BL / 6 mice. Separated cells were resuspended in RPMI-1640 medium, splenocytes isolated from one mouse were treated with mitomycin C to stop cell division, washed several times with RPMI-1640 medium, Respectively. Each of the cells was mixed and added to 96-well plates at a cell density of 1 × 10 ⁶ cells / well. ConA (ConA, concanavalin A) was added and the cells were cultured for 4 days in 37% and 5% CO ₂ . The XTT reagent was added 4 hours before the end of the culture of the spleen cells, and after 4 hours of incubation, the absorbance was measured at 490 nm. Immunosuppressive ability was determined at a rate that inhibited cell differentiation compared to the control.

[Equation 1]

Immunosuppressive ability (%) = (ODmax-ODsample / ODmax-ODmin) 100

In the above equation (1), ODmax is the degree of cell proliferation when ConA and medium are added,

ODmin indicates the degree of cell proliferation in the case of addition of ConA without addition of ConA, and ODsample indicates the degree of proliferation of the cell when ConA and the sample are simultaneously added.

Table 1 shows the results of measuring the immunosuppressive ability of cyclosporine A and cyclophosphamide with different concentration of the fungus, guava, and citrated mixed extract as a positive control group. The concentration of 5 g / ml of immunoglobulin, guava, and ganoderma showed a 57% immunosuppressive ability. As the concentration increased, the immunosuppressive ability gradually increased. At 100 g / ml, 82.4% Respectively. The positive control group, cyclosporin A, was used. However, the present inventors of the present invention showed that the mixed extract of guava and guar gum was lower in immunosuppressive ability than cyclosporin A at the same concentration by 10%. However, considering that it is a natural extract, Activity.

As described above, the present inventors of the present invention, Guava,

Suppression of nitric oxide production and modulation of cytokine secretion

And the epidermis of the stratum corneum sedation, erythema reduction, itching annihilation effect, antibacterial action, cotton

Reverse inhibitory and regulatory effects, inflammatory mediator suppression effects such as acne

It can be usefully used by improving or treating dermatitis.

Table 1. Immunosuppressive effect (%) by mixed lymphocyte reaction experiment of Jibuja, Guava, and senile mixed extracts

Table 2. Ability to inhibit the formation of nitrogen monoxide (NO) from the extracts of guinea pigs, Guava,

<1-1> Measurement of cytokine secretion inhibition ability of mixed extract of gujava, guava, and senescence

Splenocytes from BALB / c mice were separated as in Experimental Example <1-1> and inoculated into 96-well plates at 1 × 10 ⁶ cells / well. 1 g of ConA and samples were added thereto, followed by culturing for 3 days in a 37%, 5% CO ₂ environment. After incubation, the culture supernatant was transferred to a new plate and stored at -20 until cytokine was measured. Cytokines secreted into the medium were assayed using a mouse IFN-ELISA kit and an IL-4 ELISA kit from Biosource according to the manufacturer's instructions and quantitated the amount of cytokine secreted at 405 nm. The effects of dietary supplementation, Guava, and senescence mixed extracts on the cytokine secretion ability are shown in [Table 3-A and Table 3-B]. As shown in [Table 3, A and B], the positive control groups cyclosporin and dexamethasone showed a decrease in interleukin 4 and gamma interferon as the concentration increased. In addition, it was confirmed that secretion of interleukin-4 was decreased as the concentration of the extract was increased, and that the secretion ability of gamma interferon was also decreased in a concentration-dependent manner. As a result, the present inventors of the present invention, guava, Cytokine control ability was observed.

Table 3-A. The secretion of interleukin-4, a cytokine secreted by T-cells,

Table 3-B. Effect of lipoprotein, guava, and citrated mixed extract on the secretion of gamma-interferon, a cytokine secreted from T-cells (absorbance at 405 nm)

Experimental Example 2 Experimental Experiment of Skin Disease Treatment Experiment Participants Using Mixed Fermented Extracts of Golden Rice, Cinnamon, Cinnamon, Yugenpia, Sambucoptera, Quercus mongolica, The effect of the mixed fermentation extracts of Yugunpi, Sirius japonica, Quercus mongolica, Quercus mongolica, Chinchon mushroom, Wanbai, Huangbai, Huangliao, and golden mixed fermentation extracts was tested for 18 participants for 3 months from March to May 2012. These 18 children consisted of 10 children under 13, 10 children under 13-20, and 10 adults. Each experimental participant was informed about the use of the present invention of the present invention, guava, and regulated mixed extract, and the extract was distributed to the participants for 2 weeks. The application areas of the extract were arms, legs, calves, , Whole face, back, whole body, soles and so on. The main skin diseases of these participants were 5 atopic dermatitis, 15 acne, 7 general dermatitis and 3 athlete's foot, as shown in Table 4 below, and the male to female sex ratio was 8:10. Participants were asked to describe the degree of symptom relief before and after use by the participant or the guardian in the case of the child.

[Table 4] Improvement of dermatological condition of mixed extract of guideline, Guava,

As shown in Table 4, the experimental results showed that the symptom was alleviated within one week in most of the participants. Regeneration effect of epidermis was observed as mitigating symptoms of the stratum corneum, reduction of itching and erythema, and reduction of erythema. therefore,

The present inventors have confirmed that the branch extract, guava, and regulated mixed extract are effective for other skin diseases such as acne skin disease and atopy.

Claims (1)

A pharmaceutical composition for improving or treating a skin disease selected from the group consisting of atopic dermatitis, acne, general dermatitis, and athlete's foot, which comprises as an active ingredient, a lipid extracted from water, an alcohol or an aqueous alcohol solution, guava, .